MiR-338-5p indirectly regulate BAFF signal by targeting TRAF3 during renal allograft antibody-mediated rejection (P2200)

Abstract

Abstract Objective: To investigate the regulation mechanism of B cell activating factor (BAFF) signal during antibody-mediated renal allograft rejection (ABMR), microRNAs chip assay and further studies were carried out. Methods: The renal allograft tissues were diagnosed according to Banff'2005 criteria. MicroRNA chip assay was done (tested group: 4 ABMR tissues with high expression of BAFF and C4d; controlled group: 4 IF-TA tissues with no expression of BAFF and C4d). 20 other renal allograft tissues were chosen for differentially expression microRNAs testification, and TRAF3, BAFF and BAFF-R detection by IHC. Dual-lucifirase assay and further functional experiments were taken. Results: microRNA chip assay indicated that miR-200c, miR-30c, let-7b, miR-30b, and 7 other microRNAs were differentially up-regulated and only miR-338-5p was significantly down-regulated. Combing with research background, bioinformatics analysis suggested that TRAF3 was the target gene of miR-338-5p and only regulated by miR-338-5p, which was testified by luciferase assay. The real-time PCR data indicated that miR-338-5p was significantly down-regulated in ABMR tissues, and inversely correlated with BAFF, BAFF-R and TRAF3 (these three molecules high expressed in ABMR tissues). And miR-338-5p mimics and inhibitors can seperately stimulate and inhibit IgG secretion by tonsil B cells in vitro. Conclusions: miR-338-5p participate in ABMR by indirectly regulating BAFF signal via targeting TRAF3.